JAK2 (Janus kinase 2)

Persistent unexplained thrombocytosis with prior arterial thrombosis should raise suspicion for an occult myeloproliferative neoplasm, whereas postoperative HIT remains a clinical consideration despite negative functional assays, particularly in the context of potent P2Y12 receptor inhibition.

In the latter, the observed CV risk might stem from failure of JAKi to fully inhibit prothrombotic pathways induced by cytokines (TNF and IL-17) and the potential dose-related vascular toxicity. Understanding these binary effects will provide new insights into the divergent CV impact of JAKi.

While these characteristics may contribute to therapeutic action, dose-dependent hepatotoxicity has been reported, highlighting critical translational challenges and the need for formulation advances and safety optimization. Future research should emphasize pharmacokinetic-pharmacodynamic modeling, nano-delivery systems, toxicity profiling, and well-designed clinical studies to support its translational development.

Critically, most mechanistic findings remain at the preclinical or retrospective validation stage, with no markers yet approved for routine clinical use. Future work must prioritize longitudinal paired clinical samples, standardized analytic assays for dynamic biomarkers, and the integration of functional models (organoids, microfluidic systems), multi-omics technologies (single-cell sequencing, spatial transcriptomics), and liquid-biopsy approaches to translate mechanistic discoveries into clinically actionable predictive tools and therapeutic strategies.

ORR was 57%, 20% and 25% in patients treated by intensive chemotherapy (IC), hypomethylating agents (HMA) and BSC (including low intensity treatments as hydroxyurea and low-dose cytarabine), respectively. We observed poor outcome using IC or HMA encouraging us to propose new clinical trials in this specific subgroup. Only ASCT was able to improve prognosis.

P=N/A, N=500, Not yet recruiting, Weizmann Institute of Science

CML and PV exhibited distinct cytokine-driven transcriptional signatures, whereas ET and PMF exhibited minimal alterations. These findings support the clinical utility of NanoString technology for bone marrow specimens and highlight disease-specific immune pathways as potential diagnostic biomarkers in MPNs.

Linezolid acts as a JAK2 V617F IZselective inhibitor in PV mouse models and PV patient samples while sparing wildIZtype hematopoiesis. Linezolid acts directly on JAK2 V617F hematopoietic stem cells.

Our findings indicate that although OGM excels at resolving complex structural variants, CMA remains essential for detecting copy-neutral events. Until OGM achieves improved sensitivity for CN-LOH, an integrated approach utilizing conventional cytogenetics, CMA, NGS, and OGM provides the most reliable framework for comprehensive genomic assessment across cancer types.

This study provides one of the first extensive characterizations of PV in southern Colombia, confirming internationally recognized clinical features, including advanced age at diagnosis, increased prevalence of cardiovascular comorbidities, and a predominance of high-risk classification. The low rate of finding JAK2 mutations suggests that molecular testing may not be as easy to get as it could be. Even if the treatment followed the guidelines, the risk of recurrence and thrombosis remained, showing that PV is a long-term and worsening condition. These findings highlight the urgent need to expand access to molecular diagnostics, develop tailored risk-adapted medicines, and initiate prospective multicenter studies in Latin America to optimize outcomes and quality of life in PV.

In conclusion, this study unveils the RNF138-hnRNPA0-WWOX axis as a driver of JAK2/STAT3 activation, leading to both chemoresistance and immune evasion in NPC. This work positions RNF138 as a valuable biomarker to guide individualized chemotherapy, and highlights JAK inhibitors as a potential targeted therapy for NPC patients.

Management of thromboembolic event requires cytoreductive therapy and, depending on the site of thrombosis, antiplatelet therapy, and/or anticoagulation. Our review provides an overview of essential thrombocythemia, polycythemia vera, and primary myelofibrosis, as well as the hemostatic disorders associated with these conditions, focusing on diagnostic approaches and the prophylaxis and management of thromboembolic and bleeding complications.